Prognostic implications of systemic immune-inflammation index in myocardial infarction patients with and without diabetes: insights from the NOAFCAMI-SH registry.

BACKGROUND: It is well-known that systemic inflammation plays a crucial role in the pathogenesis and prognosis of acute myocardial infarction (AMI). The systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio) is a novel index that is used for the characterization of the severity of systemic inflammation. Recent studies have identified the high SII level as an independent predictor of poor outcomes in patients with AMI. We aimed to investigate the prognostic implications of SII in AMI patients with and without diabetes mellitus (DM). METHODS: We included 2111 patients with AMI from February 2014 to March 2018. Multivariable Cox regression analyses were performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause death and cardiovascular (CV) death. Multiple imputation was used for missing covariates. RESULTS: Of 2111 patients (mean age: 65.2 ± 12.2 years, 77.5% were males) analyzed, 789 (37.4%) had DM. Generalized additive model analyses showed that as the SII increased, the C-reactive protein and peak TnT elevated while the LVEF declined, and these associations were similar in patients with and without DM. During a median of 2.5 years of follow-up, 210 all-cause deaths and 154 CV deaths occurred. When treating the SII as a continuous variable, a higher log-transformed SII was significantly associated with increased all-cause mortality (HR: 1.57, 95%CI: 1.02-2.43) and CV mortality (HR: 1.85, 95%CI 1.12-3.05), and such an association was also significant in the diabetics (HRs and 95%CIs for all-cause death and CV death were 2.90 [1.40-6.01] and 3.28 [1.43-7.57], respectively) while not significant in the nondiabetics (Pinteraction for all-cause death and CV death were 0.019 and 0.049, respectively). Additionally, compared to patients with the lowest tertiles of SII, those with the highest tertiles of SII possessed significantly higher all-cause mortality (HR: 1.82, 95%CI 1.19-2.79) and CV mortality (HR: 1.82, 95%CI 1.19-2.79) after multivariable adjustment, and this relationship remained pronounced in the diabetics (HRs and 95%CIs for all-cause death and CV death were 2.00 [1.13-3.55] and 2.09 [1.10-3.98], respectively) but was not observed in the nondiabetics (HRs and 95%CIs for all-cause death and CV death were 1.21 [0.75-1.97] and 1.60 [0.89-2.90], respectively). Our restricted cubic splines analyses indicated a pronounced linear association between SII and mortality only in diabetics. CONCLUSIONS: In AMI patients with DM, high SII is an independent predictor of poor survival and may be helpful for patient's risk stratification.

Association of stress hyperglycemia ratio with in-hospital new-onset atrial fibrillation and long-term outcomes in patients with acute myocardial infarction.

AIMS: To investigate the predictive value and prognostic impact of stress hyperglycemia ratio (SHR) for new-onset atrial fibrillation (NOAF) complicating acute myocardial infarction (AMI). MATERIALS AND METHODS: This retrospective study included 2145 AMI patients without AF history between February 2014 and March 2018. SHR was calculated using fasting blood glucose (mmol/L)/[1.59*HbA1c (%)-2.59]. The association between SHR and post-MI NOAF was assessed with multivariable logistic regression analyses. The primary outcome was a composite of cardiac death, heart failure hospitalisation, recurrent MI, and ischaemic stroke (MACE). Cox regression-adjusted hazard ratios with 95% confidence intervals (CI) were estimated for MACE. RESULTS: A total of 245 (11.4%) patients developed NOAF. In the multivariable logistic regression analyses, SHR (each 10% increase) was significantly associated with increased risks of NOAF in the whole population (OR: 1.05, 95% CI: 1.01-1.10), particularly in non-diabetic individuals (OR:1.08, 95% CI: 1.01-1.17). During a median follow-up of 2.7 years, 370 (18.5%) MACEs were recorded. The optimal cut-off value of SHR for MACE prediction was 1.119. Patients with both high SHR (≥1.119) and NOAF possessed the highest risk of MACE compared to those with neither high SHR nor NOAF after multivariable adjustment (HR: 2.18, 95% CI: 1.39-3.42), especially for diabetics (HR: 2.63, 95% CI: 1.41-4.91). Similar findings were observed using competing-risk models. CONCLUSIONS: SHR is an independent predictor of post-MI NOAF in non-diabetic individuals. Diabetic patients with both high SHR and NOAF had the highest risk of MACE, suggesting that therapies targeting SHR may be considered in these patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03533543.

Prognostic impact of stress hyperglycemia ratio in acute myocardial infarction patients with and without diabetes mellitus.

BACKGROUND AND AIMS: Stress hyperglycemia ratio (SHR) is associated with increased in-hospital morbidity and mortality in patients with acute myocardial infarction (AMI). We aimed to investigate the impact of stress "hyperglycemia" on long-term mortality after AMI in patients with and without diabetes mellitus (DM). METHODS AND RESULTS: We included 2089 patients with AMI between February 2014 and March 2018. SHR was measured with the fasting glucose divided by the estimated average glucose derived from glycosylated hemoglobin (HbA1c). The primary endpoint was all-cause death. Of 2 089 patients (mean age: 65.7 ± 12.4, 76.7% were men) analyzed, 796 (38.1%) had DM. Over a median follow-up of 2.7 years, 141 (6.7%) and 150 (7.2%) all-cause deaths occurred in the diabetic and nondiabetic cohorts, respectively. Compared with participants with low SHR (<1.24 in DM; <1.14 in non-DM), the hazard ratios and 95% confidence intervals for those with high SHR (≥1.24 in DM; ≥1.14 in non-DM) for all-cause mortality were 2.23 (1.54-3.23) and 1.79 (1.15-2.78); for cardiovascular mortality were 2.42 (1.63-3.59) and 2.10 (1.32-3.35) in DM and non-DM subjects, respectively. The mortality prediction was improved in the diabetic individuals with the incorporation of SHR into the Global Registry of Acute Coronary Events (GRACE) score, showing an increase in a continuous net reclassification index of 0.184 (95%CI: 0.003-0.365) and an absolute integrated discrimination improvement of 0.014 (95%CI: 0.002-0.025). CONCLUSION: The improvement in the prediction of long-term mortality beyond the GRACE score indicates the potential of SHR as a biomarker for post-MI risk stratification among patients with DM. REGISTRATION NUMBER FOR CLINICAL TRIALS: NCT03533543.

ZPI prevents ox-LDL-mediated endothelial injury leading to inhibition of EndMT, inflammation, apoptosis, and oxidative stress through activating Pi3k/Akt signal pathway.

Oxidized low-density lipoprotein (ox-LDL)-mediated endothelial dysfunction exerts an essential role in the development of atherosclerosis. Protein Z-dependent protease inhibitor (ZPI), a member of the serine protease inhibitor superfamily, could inhibit the function of activated coagulation factor X (FXa) via interaction with protein Z (PZ). Studies have pointed out that ZPI was statistically related to atherosclerotic diseases, which may have a robust cardiovascular protective effect. However, the underlying mechanism of ZPI on ox-LDL-mediated endothelial injury requires further elucidation. Human umbilical vein endothelial cells (HUVECs) were treated with ox-LDL (100 µg/ml) and ZPI (10 µg/ml). Cell viability was measured by the Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis, oxidative stress, and endothelial-to-mesenchymal transition (EndMT) were analyzed by immunofluorescence (IF). Cell migration was measured using a wound-healing assay. Quantitative real-time polymerase chain reaction and western blot analysis were performed to determine messenger RNA and protein expression. Ox-LDL (100 µg/ml, 48 h) significantly reduced cell viability and migration, increased EndMT, inflammation, apoptosis, and oxidative stress. The related protein expression of phosphatidylinositol 3 kinase/protein kinase B (Pi3k/Akt) signal pathway in HUVECs was also simultaneously decreased. We also discovered that ZPI treatment could prevent ox-LDL-mediated endothelial injury through the improvement of cell viability and alleviation of apoptosis, oxidative stress, EndMT, and inflammation. Thus, the protective effect of ZPI on HUVECs may be mediated by activation of the Pi3k/Akt signal pathway. ZPI may exert an important protective role in HUVECs dysfunction triggered by ox-LDL via activation of the Pi3k/Akt signal pathway. Therefore, ZPI may possess potential therapeutic effects on atherosclerotic endothelial injury-related diseases.

Long-term impact of the burden of new-onset atrial fibrillation in patients with acute myocardial infarction: results from the NOAFCAMI-SH registry.

AIMS: We aimed to investigate the prognostic impact of the burden of new-onset atrial fibrillation (NOAF) on long-term cardiovascular outcomes in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: This retrospective analysis consecutively included patients without a documented atrial fibrillation (AF) history who admitted for AMI at Shanghai Tenth People's Hospital between February 2014 and March 2018. Atrial fibrillation burden was measured as the percentage of time spent in AF, and its optimal cut-off value of 10.87% was identified by X-tile software. Of 2399 patients (mean age: 65.8 years, 76.6% of men), 278 (11.6%) developed NOAF during hospitalization. During a median follow-up of 2.7 years, the incidence of all-cause death was 3.19, 9.00, and 17.41 per 100 person-years in the sinus rhythm (SR), low-burden (AF burden ≤ 10.87%), and high-burden (AF burden > 10.87%) groups, respectively. After adjustment for confounders, it was the high-burden NOAF [hazard ratio (HR): 1.94, 95% confidence interval (CI): 1.28-2.95] rather than the low-burden one (HR: 1.47, 95% CI: 0.97-2.21) that was significantly associated with increased mortality compared with SR. Concordant results were obtained in our propensity score-matched analyses [2.55 (1.57-4.16) and 1.32 (0.85-2.05) for high- and low-burden NOAF, respectively). In addition, post-myocardial infarction NOAF was associated with an increased risk of heart failure irrespective of its burden. Only those high-burden individuals were at heightened risk of ischaemic stroke. The restricted cubic spline curves illustrated a dose-response relationship of NOAF burden with outcomes. CONCLUSION: In patients with NOAF complicating AMI, high AF burden was strongly associated with long-term outcomes.

Inhibition of miR-25 attenuates doxorubicin-induced apoptosis, reactive oxygen species production and DNA damage by targeting PTEN.

Background: Doxorubicin (DOX) is one of the widely used anti-cancer drugs, whereas it can induce irreversible cardiac injury in a dose-dependent manner which limits its utility in clinic. Our study aimed to investigate the relationship between miR-25 and DOX-induced cardiac injury and its underlying mechanism. Methods: Mice and H9c2 cells were exposed to DOX. The overexpressed or knockdown of miR-25 in H9c2 cells was achieved by miR-25 mimic or inhibitor and the efficiency of transfection was identified by qRT-PCR or Western blotting. Cell viability, apoptotic cell rate, and levels of apoptosis-related proteins were determined by CCK-8, flow cytometry, and Western blotting, respectively. Furthermore, Western blotting and immunofluorescence staining (IF) were performed to assess the expression levels of reactive oxygen species and degree of DNA damage. Results: As a result, DOX significantly upregulated miR-25 expression in mice and H9c2 cells and reduced cell viability and increased cell apoptosis in vitro and in vivo. miR-25 overexpression expedited cell injury induced by DOX in H9c2 cells demonstrated by the increased cell apoptosis and reactive oxygen species (ROS) production, whereas miR-25 inhibition attenuated the cell injury. Furthermore, miR-25 negatively controlled the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). Intervention the expression of PTEN using si-PTEN reversed the beneficial effects of miR-25 inhibition on DOX-injured H9c2 cells. Conclusion: In conclusion, this study demonstrated that miR-25 is involved in DOX-induced cell damage through the regulation of PTEN expression.

MicroRNA-320 targeting neuropilin 1 inhibits proliferation and migration of vascular smooth muscle cells and neointimal formation.

This study shows that microRNA-320 (miR-320) is associated with many important cell functions, including cell differentiation, proliferation, migration, and apoptosis. However, the role of miR-320 in vascular smooth muscle cells (VSMCs) and proliferative vascular diseases is still completely unclear. In our study, we found that the expression of miR-320 in human VSMCs after PDGF stimulation was significantly down-regulated in time- and dose-dependent manner. Function analyses identified that miR-320 could inhibit the proliferation and migration of VSMCs in both basal and PDGF-stimulated conditions. Furthermore, Neuropilin 1 (NRP1) was demonstrated as a direct target of miR-320 in Luciferase reporter assays and miR-320 overexpression inhibited the expression of NRP1 with or without PDGF treatment. Finally, miR-320 was markedly decreased in mice carotid arteries after ligated injury, while the restoration of miR-320 via Ad-miR-320 attenuated neointimal hyperplasia by declining the NRP1 expression. The results confirmed that miR-320 regulated proliferation and migration of VSMCs and neointimal formation by targeting NRP1. These novel findings implied that the regulation of NRP1 expression by miR-320 has important significance in the early diagnosis and treatment of proliferation vascular diseases.

Elevated plasma S100A1 level is a risk factor for ST-segment elevation myocardial infarction and associated with post-infarction cardiac function.

AIM: To investigate the association between plasma S100A1 level and ST-segment elevation myocardial infarction (STEMI) and potential significance of S100A1 in post-infarction cardiac function. METHODS: We examined the plasma S100A1 level in 207 STEMI patients (STEMI group) and 217 clinically healthy subjects for routine physical examination without a history of coronary artery disease (Control group). Baseline characteristics and concentrations of relevant biomarkers were compared. The relationship between S100A1 and other plasma biomarkers was detected using correlation analysis. The predictive role of S100A1 on occurrence of STEMI was then assessed using multivariate ordinal regression model analysis after adjusting for other covariates. RESULTS: The plasma S100A1 level was found to be significantly higher (P<0.001) in STEMI group (3197.7±1576.0 pg/mL) than in Control (1423.5±1315.5 pg/mL) group. Furthermore, the correlation analysis demonstrated plasma S100A1 level was significantly associated correlated with hypersensitive cardiac troponin T (hs-cTnT) (r = 0.32; P < 0.001), creatine kinase MB (CK-MB) (r = 0.42, P < 0.001), left ventricular eject fraction (LVEF) (r = -0.12, P = 0.01), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (r = 0.61; P < 0.001) and hypersensitive C reactive protein (hs-CRP) (r = 0.38; P < 0.001). Moreover, the enrolled subjects who with a S100A1 concentration ≤ 1965.9 pg/mL presented significantly better cardiac function than the rest population. Multivariate Logistic regression analysis revealed that S100A1 was an independent predictor for STEMI patients (OR: 0.671, 95% CI 0.500-0.891, P<0.001). In addition, higher S100A1 concentration (> 1965.9 pg/mL) significantly increased the risk of STEMI as compared with the lower level (OR: 6.925; 95% CI: 4.15-11.375; P<0.001). CONCLUSION: These results indicated that the elevated plasma S100A1 level is an important predictor of STEMI in combination with several biomarkers and also potentially reflects the cardiac function following the acute coronary ischemia.

Lipid oxidation inactivates the anticoagulant function of protein Z-dependent protease inhibitor (ZPI).

Lipid oxidation due to oxidative stress plays an important role in the pathogenesis of inflammatory and thrombotic cardiovascular diseases. Several findings suggest that lipid peroxidation can alter the function of coagulation proteins and contribute to a hypercoagulable state, but the molecular mechanisms are unclear. Here, we report that oxidized phospholipids suppress the anticoagulant function of the serpin, protein Z-dependent protease inhibitor (ZPI), a specific inhibitor of membrane-associated factor Xa (FXa) that requires protein Z (PZ), phospholipid, and calcium as cofactors. We found that this suppression arises from a diminished ability of the oxidized membrane to function as a cofactor to promote ZPI inhibition of membrane-bound FXa, due fully or in part to the susceptibility of the bound ZPI-PZ complex to oxidative inactivation. Surprisingly, free ZPI was also susceptible to inactivation by oxidized membrane vesicles in the absence of calcium. Oxidized vesicles containing both phosphatidylserine and polyunsaturated fatty acids were required to promote inactivation of the ZPI-PZ complex or free ZPI, indicating that binding of the PZ-complexed or free ZPI to peroxide-modified phospholipid vesicles mediates the inactivation. Heparin protected the ZPI-PZ complex and free ZPI from inactivation, suggesting that blocking the heparin-binding site on ZPI interferes with ZPI binding to lipid or to PZ. This was confirmed by direct lipid-binding experiments. Native PAGE indicated that oxidization induced dissociation of the ZPI-PZ complex and increased the negative charge of ZPI. We conclude that compromised ZPI anticoagulant function could contribute to thrombus initiation and growth in oxidative stress-induced cardiovascular diseases.

Rac1 promotes the survival of H9c2 cells during serum deficiency targeting JNK/c-JUN/Cyclin-D1 and AKT2/MCL1 pathways.

Rac1, known as a "molecular switch", plays a crucial role in plenty of cellular processes. Rac1 aggravates the damage of myocardial cells in the process of myocardial ischemia-reperfusion during myocardial infarction through activating the NADPH oxidase and bringing about the reactive oxygen species(ROS) generation. Myocardial ischemia and hypoxia are the basic pathogenesis of myocardial infarction and the underlying mechanisms are intricate and varied. Moreover, the regulatory effect of Rac1 on myocardial cells in the condition of serum starvation and the potential mechanisms are still incompletely undefined. Therefore, heart-derived H9c2 cells cultured in 0% serum were used to mimic ischemic myocardial cells and to clarify the role of Rac1 in H9c2 cells and the underlying mechanisms during serum deficiency. After Rac1 was knocked down using specific siRNA, cell apoptosis was assessed by flow cytometry assay and cell proliferation was detected by CCK-8 assay and EdU assay. In addition, the expression and activation of protein in related signaling pathway were detected by Western blot and siRNAs was used to testify the signaling pathways. Our results indicated that Rac1 inhibited apoptosis, promoted proliferation and cell cycle progression of H9c2 cells during serum deficiency. We concluded that Rac1 inhibited apoptosis in an AKT2/MCL1 dependent way and promoted cell proliferation through JNK/c-JUN/Cyclin-D1.

The influence of individual socioeconomic status on the clinical outcomes in ischemic stroke patients with different neighborhood status in Shanghai, China.

Objective: Socioeconomic status (SES) is being recognized as an important factor in both social and medical problems. The aim of present study is to examine the relationship between SES and ischemic stroke and investigate whether SES is a predictor of clinical outcomes among patients with different neighborhood status from Shanghai, China. Methods: A total of 471 first-ever ischemic stroke patients aged 18-80 years were enrolled in this retrospective study. The personal SES of each patient was evaluated using a summed score derived from his or her educational level, household income, occupation, and medical reimbursement rate. Clinical adverse events and all-cause mortality were analyzed to determine whether SES was a prognostic factor, its prognostic impact was then assessed based on different neighborhood status using multivariable Cox proportional hazard models after adjusting for other covariates. Results: The individual SES showed a significant positive correlation with neighborhood status (r = 0.370; P < 0.001). The incidence of clinical adverse events and mortality were significantly higher in low SES patients compared with middle and high SES patients (P = 0.001 and P = 0.037, respectively). After adjusting other risk factors and neighborhood status, Kaplan-Meier analysis showed clinical adverse events and deaths were still higher in the low SES patients (all P < 0.05). Multivariate Cox regression analysis demonstrated that both personal SES and neighborhood status are independent prognostic factors for ischemic stroke (all P < 0.05). Besides, among patients with low and middle neighborhood status, lower individual SES was significantly associated with clinical adverse events and mortality (all P < 0.05). Conclusion: Both individual SES and neighborhood status are significantly associated with the prognosis after ischemic stroke. A lower personal SES as well as poorer neighborhood status may significantly increase risk for adverse clinical outcomes among ischemic stroke patients.

MiR-449a suppresses the epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma by multiple targets.

BACKGROUND: Increasing evidence indicates that Epithelial-mesenchymal transition (EMT) can be regulated by microRNAs (miRNAs). MiR-449a is a liver abundant miRNA. However, the role of miR-449a in the metastasis of hepatocellular carcinoma (HCC) remains largely unknown. METHODS: The expression levels of miR-449a were first examined in HCC cell lines and tumour tissues by real-time PCR. The in vitro and in vivo functional effect and underlying molecular mechanisms of miR-449a were examined further. RESULTS: In the present study, we found that miR-449a was significantly decreased in HCC cells and tissues, especially in those with the portal vein tumor thrombus. In HCC cell lines, stable overexpression of miR-449a was sufficient to inhibit cell motility in vitro, and pulmonary metastasis in vivo. In addition, ectopic overexpression of miR-449a in HCC cells promoted the expression of epithelial markers and reduced the levels of mesenchymal markers. Further studies revealed that the reintroduction of miR-449a attenuated the downstream signaling of Met, and consequently reduced the accumulation of Snail in cell nucleus by targeting the 3'-untranslated regions (3'-UTR) of FOS and Met. CONCLUSIONS: Our data highlight an important role of miR-449a in the molecular etiology of HCC, and implicate the potential application of miR-449a in cancer therapy.

Resveratrol suppresses oxidised low-density lipoprotein-induced macrophage apoptosis through inhibition of intracellular reactive oxygen species generation, LOX-1, and the p38 MAPK pathway.

BACKGROUND/AIM: Resveratrol (RSV) may have therapeutic potential for various diseases. Here we investigated the effect of RSV on oxidised low-density lipoprotein- (ox-LDL) induced apoptosis in RAW264.7 macrophages. METHODS: Apoptosis of macrophages following incubation with ox-LDL (with or without RSV pre-treatment) was detected by flow cytometry. Western blotting was used to assess the protein expression of Bax, Bcl-2, and caspase-3 as well as ox-LDL receptor 1 (LOX-1) and p38 mitogen-activated protein kinase (MAPK) phosphorylation. Reactive oxygen species (ROS) generation was evaluated by 2', 7'-dichlorofluorescein diacetate, and JC-1 probe was used to determine the mitochondrial transmembrane potential of cells. RESULTS: Ox-LDL significantly reduced viability and increased the rate of apoptosis (P < 0.05) in RAW264.7 cells. However, pre-treatment with RSV resulted in a remarkable decrease in this apoptotic effect. Moreover, ox-LDL caused the up-regulation of Bax and the down-regulation of Bcl-2, as well as the activation of caspase-3. Expression of LOX-1, phosphorylation of p38 MAPK, and intracellular ROS production also increased after ox-LDL stimulation. Strikingly, these effects were abolished by pre-treatment of cells with RSV. CONCLUSION: RSV suppresses ox-LDL-induced macrophage apoptosis. These beneficial effects might be exerted through inhibition of ROS generation, LOX-1, and the p38 MAPK signalling pathway.

The basic social medical insurance is associated with clinical outcomes in the patients with ST-elevation myocardial infarction: a retrospective study from Shanghai, China.

OBJECTIVE: Several social economic factors play important roles in treatments of ST-elevation myocardial infarction (STEMI) and finally influence the clinical outcomes. The basic social medical insurance (BSMI) is an important economic factor in China's medical system. However, the impact of BSMI on clinical outcomes in STEMI patients has not been explored yet. The aim of this study is to investigate whether BSMI is a predictor of clinical outcomes in the patients with STEMI in Shanghai, China. MATERIAL AND METHODS: In this retrospective study, 681 STEMI patients from different areas in Shanghai were classified into four groups: new rural cooperative medical scheme (NCMS) group, urban resident basic medical insurance scheme (URBMI) group, urban employee basic medical insurance scheme (UEBMI) group and UNINSURED group, major adverse events (cardiac death, nonfatal reinfarction, clinically driven target lesion revascularization/target vessel revascularization, stroke, heart failure) were regarded as study endpoints to determine whether BSMI was a prognostic factor. RESULTS: During a mean follow-up of 36 months, the incidence of major adverse events was significantly higher in NCMS patients (64; 38.8%) compared with the other groups: URBMI (47; 24.6%); UEBMI (28; 15.6%); UNISURED (40; 27.6%). Similarly, cardiac mortality was also higher in NCMS group (19; 11.5%). A Kaplan-Meier survival analysis revealed significantly lower event-free survival rate for major adverse events (p < 0.001) and cardiac mortality (p = 0.01) in NCMS group. Multivariate Cox regression analysis revealed that BSMI was an important prognostic factor in STEMI patients. CONCLUSION: These results demonstrate that BSMI is closely associated with the major adverse events-free survival rate at 36-month follow-up in the STEMI patients under the current policies in Shanghai, China.

Effects of obstructive sleep apnea on cardiac function and clinical outcomes in Chinese patients with ST-elevation myocardial infarction.

AIM: The objective of this study was to investigate the influence of OSA on cardiac function in Chinese patients with ST-elevation myocardial infarction (STEMI) and determine the prognostic impact of OSA among these patients. METHODS: In this retrospective study, 198 STEMI patients were enrolled. Doppler echocardiography was performed to detect the effect of OSA on cardiac function. Major adverse cardiac events (MACE) and cardiac mortality were analyzed to determine whether OSA was a clinical prognostic factor; its prognostic impact was then assessed adjusting for other covariates. RESULTS: The echocardiographic results showed that the myocardium of STEMI patients with OSA appeared to be more hypertrophic and with a poorer cardiac function compared with non-OSA STEMI patients. A Kaplan-Meier survival analysis revealed significantly higher cumulative incidence of MACE and cardiac mortality in the OSA group compared with that in the non-OSA group during a mean follow-up of 24 months. Multivariate Cox regression analysis revealed that OSA was an independent risk factor for MACE and cardiac mortality. CONCLUSION: These results indicate that the OSA is a powerful predictor of decreased survival and exerts negative prognostic impact on cardiac function in STEMI patients.

Prognostic impact of new-onset atrial fibrillation in myocardial infarction with and without improved ejection fraction.

AIMS: Improvement in left ventricular ejection fraction (impEF) often presents in contemporary acute myocardial infarction (AMI) patients. New-onset atrial fibrillation (NOAF) during AMI is an important predictor of subsequential heart failure (HF), while its impact on the trajectory of post-MI left ventricular ejection fraction (LVEF) and prognostic implication in patients with and without impEF remains undetermined. We aimed to investigate the prognostic impacts of NOAF in AMI patients with and without impEF. METHODS AND RESULTS: Consecutive AMI patients without a prior history of AF between February 2014 and March 2018 with baseline LVEF ≤ 40% and had ≥1 LVEF measurement after baseline were included. ImpEF was defined as a baseline LVEF ≤ 40% and a re-evaluation showed both LVEF > 40% and an absolute increase of LVEF ≥ 10%. Persistently reduced EF (prEF) was defined as the second measurement of LVEF either ≤40% or an absolute increase of LVEF < 10%. The primary endpoint was a major adverse cardiac event (MACE) that was composed of cardiovascular death and HF hospitalization. Cox regression analysis and competing risk analysis were performed to assess the association of post-MI NOAF with MACE. Among 293 patients (mean age: 66.6 ± 11.3 years, 79.2% of males), 145 (49.5%) had impEF and 67 (22.9%) developed NOAF. Higher heart rate (odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.73-0.97; P = 0.015), prior MI (OR: 0.25, 95% CI: 0.09-0.69; P = 0.008), and STEMI (OR: 0.40, 95% CI: 0.21-0.77; P = 0.006) were independent predictors of post-MI impEF. Within up to 5 years of follow-up, there were 22 (15.2%) and 53 (35.8%) MACE in patients with impEF and prEF, respectively. NOAF was an independent predictor of MACE in patients with impEF (hazard ratio [HR]: 7.34, 95% CI: 2.49-21.59; P < 0.001) but not in those with prEF (HR: 0.78, 95% CI: 0.39-1.55; P = 0.483) after multivariable adjustment. Similar results were obtained when accounting for the competing risk of all-cause death (subdistribution HR and 95% CIs in impEF and prEF were 6.47 [2.32-18.09] and 0.79 [0.39-1.61], respectively). CONCLUSIONS: The NOAF was associated with an increased risk of cardiovascular outcomes in AMI patients with impEF.

A New Automated Prognostic Prediction Method Based on Multi-Sequence Magnetic Resonance Imaging for Hepatic Resection of Colorectal Cancer Liver Metastases.

Colorectal cancer is a prevalent and life-threatening disease, where colorectal cancer liver metastasis (CRLM) exhibits the highest mortality rate. Currently, surgery stands as the most effective curative option for eligible patients. However, due to the insufficient performance of traditional methods and the lack of multi-modality MRI feature complementarity in existing deep learning methods, the prognosis of CRLM surgical resection has not been fully explored. This paper proposes a new method, multi-modal guided complementary network (MGCNet), which employs multi-sequence MRI to predict 1-year recurrence and recurrence-free survival in patients after CRLM resection. In light of the complexity and redundancy of features in the liver region, we designed the multi-modal guided local feature fusion module to utilize the tumor features to guide the dynamic fusion of prognostically relevant local features within the liver. On the other hand, to solve the loss of spatial information during multi-sequence MRI fusion, the cross-modal complementary external attention module designed an external mask branch to establish inter-layer correlation. The results show that the model has accuracy (ACC) of 0.79, the area under the curve (AUC) of 0.84, C-Index of 0.73, and hazard ratio (HR) of 4.0, which is a significant improvement over state-of-the-art methods. Additionally, MGCNet exhibits good interpretability.

Prognostic implications of the 4S-AF scheme to characterize new-onset atrial fibrillation after myocardial infarction.

AIMS: The 4S-AF scheme (Stroke risk [St], Symptom severity [Sy], Severity of atrial fibrillation burden [Sb], Substrate [Su]) is a novel approach for the holistic characterization of AF. We aimed to investigate the prognostic implications of the 4S-AF scheme score in acute myocardial infarction (AMI) patients with new-onset atrial fibrillation (NOAF). METHODS: We included 262 patients with post-MI NOAF who had complete data for the 4S-AF scheme evaluation between February 2014 and March 2018. The 4S-AF scheme score was calculated as a sum of each domain with a maximum of 9. The primary outcome was all-cause death. RESULTS: Of 262 patients (66.0% males, mean age 74.5 ± 10.4 years) were analyzed. The mean 4S-AF scheme score was 5.0 ± 1.6. There were 62 (27.3%) all-cause deaths within a median follow-up of 2.6 years. According to multivariable Cox regression models, each 1-point increase in the 4S-AF scheme score was significantly associated with 39% increased all-cause mortality (HR: 1.39, 95% CI: 1.16-1.67, P<0.001), which was mainly driven by the Sb (HR: 1.43, 95%CI: 1.05-1.95, P = 0.025) and Su (HR: 1.53, 95%CI: 1.17-2.02, P = 0.002) domains. Adding the 4S-AF scheme score on top of the Global Registry of Acute Coronary Events score could significantly improve its discriminative capability (C-index from 0.713 to 0.761, P = 0.039) and reclassification performance (continuous net reclassification improvement: 41.0% [95%CI: 12.5-69.6]; integrated discrimination improvement: 5.1% [95%CI: 2.2-8.1]) for all-cause mortality. CONCLUSIONS: Characterization of NOAF using the 4S-AF scheme aids in the risk stratification of AMI patients with NOAF.

TRIM21 deficiency protects against atrial inflammation and remodeling post myocardial infarction by attenuating oxidative stress.

Atrial remodeling is a major contributor to the onset of atrial fibrillation (AF) after myocardial infarction (MI). Tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin protein ligase, is associated with pathological cardiac remodeling and dysfunction. However, the role of TRIM21 in postmyocardial infarction atrial remodeling and subsequent AF remains unclear. This study investigated the role of TRIM21 in post myocardial infarction atrial remodeling using TRIM21 knockout mice and explored the underlying mechanisms by overexpressing TRIM21 in HL-1 atrial myocytes using a lentiviral vector. The expression of TRIM21 in the left atrium of the mouse MI model was significantly elevated. TRIM21 deficiency alleviated MI-induced atrial oxidative damage, Cx43 downregulation, atrial fibrosis and enlargement, and abnormalities in electrocardiogram parameters (prolongation of the P-wave and PR interval). TRIM21 overexpression in atrial myocyte HL-1 cells further enhanced oxidative damage and Cx43 downregulation, whereas these effects were reversed by the reactive oxygen species scavenger N-acetylcysteine. The findings suggest that TRIM21 likely induces Nox2 expression mechanistically by activating the NF-κB pathway, which in turn leads to myocardial oxidative damage, inflammation, and atrial remodeling.

Prognostic Significance of New-Onset Atrial Fibrillation in Heart Failure with Preserved, Mid-Range, and Reduced Ejection Fraction Following Acute Myocardial Infarction: Data from the NOAFCAMI-SH Registry.

Purpose: The prognostic impact of new-onset atrial fibrillation (NOAF) among different heart failure (HF) subtypes including HF with preserved (HFpEF, ejection fraction [EF] ≥50%), mid-range (HFmrEF, EF 40%~49%), and reduced (HFrEF, EF <40%) EF following acute myocardial infarction (AMI) remains unclear. We aimed to investigate the incidence and prognostic implication of post-MI NOAF across HF subtypes. Patients and Methods: We included 1413 patients with post-MI HF (743 with HFpEF, 342 with HFmrEF and 328 with HFrEF) between February 2014 and March 2018. NOAF was considered as patients without a preexisting AF who developed AF during the AMI hospitalization. The primary endpoint was all-cause mortality. Results: Of 1413 patients (mean age 66.8 ± 12.6 years, 72.9% men) analyzed, 200 (14.2%) developed post-MI NOAF. Patients with HFrEF were more likely to experience NOAF compared to those with HFmrEF or HFrEF (18.9%, 13.7% and 12.2% in HFrEF, HFmrEF and HFpEF, respectively; p for trend = 0.006). During a median follow-up of 28.5 months, 192 patients died (70 with HFrEF, 35 with HFmrEF and 87 with HFpEF) and 195 patients experienced HF rehospitalization (79 with HFrEF, 37 with HFmrEF and 79 with HFpEF). After multivariable adjustment, NOAF was independently associated with all-cause mortality (hazard ratio [HR]: 1.79, 95% confidence interval [CI]: 1.03-3.12) only in the HFrEF group compared to sinus rhythm (SR), whereas an increased risk of HF rehospitalization was found in all HF subtypes, particularly in HFmrEF (HR: 5.08, 95% CI: 2.29-11.25) and HFpEF (HR: 2.83 95% CI: 1.64-4.90). Conclusion: In patients with post-MI HF, NOAF carried a worse prognosis for all-cause death in the HFrEF group and for HF rehospitalization in all HF subtypes.